Abstract 4117: A non-invasive system for monitoring resistance to EGFR tyrosine kinase inhibitors with plasma DNA in lung cancer patients

Abstract

Abstract Although EGFR tyrosine kinase inhibitors (EGFR-TKIs) have great response to lung adenocarinoma with EGFR activating mutations, acquired resistance eventually developed. The half of these patients has the gatekeeper T790M mutation of EGFR in lung cancer tissue. A non-invasive mutation detection system is desired considering the difficulty in obtaining tissue specimens during disease progression_the majority of lung cancer recurrences occur in distant sites. We report a novel non-invasive monitoring system, MBP-QP (mutation-biased PCR and quenching probe) method, to detect the mutation using plasma DNA. The MBP-QP method is combined with mutated biased PCR and genotyping based on the analysis of a melting curve of probe DNA which is bound to the target mutated site using a fluorescence quenching probe. The detection limit was 2 copies of control plasmid, and 0.2 ng of genomic DNA isolated from a lung caner cell line harboring T790M. 0.3 % mutant plasmid could be detected in the mixture of plasmids inserted with EGFR exon 20 with or without T790M. With this method, T790M mutations were detected in plasma DNA of 50% of patients who acquired resistance, but not in primary EGFR-TKI non-responders, patients responding to treatment, or patients not treated with EGFR-TKI, which is consistent with the clinical course. The non-invasive MBP-QP method enabled us to monitor T790M repeatedly and will be useful for determining appropriate lung cancer treatment strategies in practice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4117. doi:10.1158/1538-7445.AM2011-4117